The Program Project's focus will be the assessment of the efficacy of sentinel lymph node dissection (SLND) compared to complete lymph node dissection (CLND) in high-risk AJCC Stage II patients enrolled in the multicenter trial (MSLT II). The MSLT II will randomize patients that are SLN histo/immuno-pathology or RT-PCR (+) for CLND. There is significant disease recurrence in melanoma patients with histopathology positive and negative SLN. The identification of micrometastasis in the lymph nodes is important in predicting disease outcome and need for adjuvant treatment. We have developed efficient multimarker quantitative realtime RT-PCR (MM qRT) assays to detect occult micrometastasis in archived paraffin-embedded (PE) SLN and have demonstrated their clinicopathologic utility. Our hypothesis is that identification of molecular risk factors in histopathology (+) SLN and detection of occult metastasis in histopathology (-) non-SLN by MM qRT can improve prediction of disease outcome. We will use MM qRT to assess PE SLN and non-SLN of patients after SLND and/or CLND with equal to or more than 5 yrs follow up. The second hypothesis is that prognostic DNA markers in primary melanomas and acellular serum can predict disease outcome. Project II Aims are: Aim I, Identification of a risk factor of recurrence in SLN histopathology (+) with more than or equal to 5 yrs follow up in the MSLT I by MM qRT of PE SLN. Aim II, Retrospective and prospective MM qRT analysis of PE non-SLN of patients who have undergone CLND in the MSLT I & II/JWCI to upstage and determine prognostic significance; and Aim III, Identification of prognostic DNA markers of primary melanomas and serum of melanoma patients to predict disease outcome in patients who have undergone SLND and/or CLND. Molecular staging and monitoring should improve the management of early-stage melanoma patients. The success of the proposed Aims will have significant impact on the assessment of SLND/CLND patients by the new AJCC staging criteria for regional tumor draining lymph nodes. The MSLT I archival and prospective MSLT II specimens along with the clinical follow up provide unique resources to validate and determine the clinicopathologic utility of the proposed studies.